Opportunistic fungal infections in dogs treated with ciclosporin and glucocorticoids: eight cases.

Glucocorticoids are the standard of care for the treatment of immune-mediated disorders, and ciclosporin is increasingly being used off-label as an adjunct immunosuppressive drug in dogs. However, opportunistic infections can develop during combination immunosuppressive regimens. This case series describes atypical fungal infections in eight dogs treated with immunosuppressive dosages of glucocorticoids and ciclosporin. The median duration of combined treatment prior to the identification of fungal infection was 31 (range, 13 to 201) days, although two dogs received glucocorticoids for prolonged periods prior to the addition of ciclosporin. The estimated prevalence of serious fungal infections with this drug combination appears to be low (approximately 1 · 67%), but these infections led directly or indirectly to death or euthanasia in five of eight (63%) dogs. These cases highlight the need for frequent clinical monitoring of dogs receiving immunosuppressive dosages of glucocorticoids and ciclosporin.

Evaluation of Iron Deficiency Using Reticulocyte Indices in Dogs Enrolled in a Blood Donor Program.

BACKGROUND: People donating blood more than twice annually are at risk of developing iron deficiency. Little is known about the iron status of dogs enrolled in blood donor programs. HYPOTHESIS: Dogs donating blood ≥6 times annually will show evidence of iron deficiency based on their reticulocyte indices. ANIMALS: Thirteen dogs enrolled in a blood donor program donating ≥6 times over the preceding 12 months and 20 healthy nondonor control dogs. METHODS: Prospective observational study. Mature red blood cell (RBC) indices, reticulocyte indices, serum iron, serum ferritin, and total iron-binding capacity (TIBC) were compared between groups. RESULTS: Packed cell volume (median 47%, range 40-52%, P < .01), hematocrit (median 46.4%, range 40.3-52.5%, P < .01), and reticulocyte count (median 16,000/µL, range 9,000-38,000/µL, P < .01) were significantly lower in the blood donor dogs. No statistically significant differences were noted in the mature RBC indices between groups. Both reticulocyte mean corpuscular volume (median 88.8 fL, range 83.4-95.5 fL, P = .03) and reticulocyte hemoglobin content (median 24.6 pg, range 23.1-26.6 pg, P < .01) were significantly lower in the blood donor group. Serum iron and ferritin were similar between groups; however, TIBC was significantly higher in the control group (median 403 µg/dL, range 225-493 µg/dL, P = .02). CONCLUSIONS: The findings in dogs donating ≥6 times annually suggest the presence of iron-deficient erythropoiesis in this population.

Serum and urine Blastomyces antigen concentrations as markers of clinical remission in dogs treated for systemic blastomycosis.

BACKGROUND: Serum and urine Blastomyces antigen concentrations can be used to diagnose blastomycosis in dogs. OBJECTIVES: Blastomyces antigen concentrations correlate with clinical remission in dogs during antifungal treatment, and detect disease relapse after treatment discontinuation. ANIMALS: 21 dogs with newly diagnosed blastomycosis monitored until clinical remission (Treatment Phase), and 27 dogs monitored over 1 year from the time of antifungal discontinuation or until clinical relapse (After Treatment Phase). METHODS: Prospective study. Dogs were monitored monthly during treatment and every 3 months after treatment discontinuation, with a complete history, physical exam, chest radiographs, and ocular exam. Urine and serum Blastomyces antigen concentrations were measured at each visit using a quantitative enzyme immunoassay. RESULTS: At enrollment in the Treatment Phase, Blastomyces antigen was positive in all 21 urine samples (100% sensitivity; 95% CI 85-100%), and in 18 of 20 serum samples (90% sensitivity; 95% CI 70-97%). At 2-4 months of treatment, urine antigen was more sensitive for clinically detectable disease (82%; CI 60-94%) than serum antigen (18%; CI 6-41%). The sensitivity of the urine test for clinical relapse was 71% (CI 36-92%), with close to 100% specificity (CI 84-100%) during after treatment surveillance in this population. CONCLUSIONS: Urine Blastomyces antigen testing has high sensitivity for active disease at the time of diagnosis and during treatment, and moderate sensitivity but high specificity for clinical relapse. Urine testing should be useful at the time of diagnosis, when treatment discontinuation is being considered, and anytime there is poor clinical response or suspicion of relapse.

Duodenal endoscopic findings and histopathologic confirmation of intestinal lymphangiectasia in dogs.

BACKGROUND: The diagnosis of intestinal lymphangiectasia (IL) has been associated with characteristic duodenal mucosal changes. However, the sensitivity and specificity of the endoscopic duodenal mucosal appearance for the diagnosis of IL are not reported. HYPOTHESIS/OBJECTIVES: To evaluate the utility of endoscopic images of the duodenum for diagnosis of IL. Endoscopic appearance of the duodenal mucosal might predict histopathologic diagnosis of IL with a high degree of sensitivity and specificity. ANIMALS: 51 dogs that underwent upper gastrointestinal (GI) endoscopy and endoscopic biopsies. METHODS: Retrospective review of images acquired during endoscopy. Dogs were included if adequate biopsies were obtained during upper GI endoscopy and digital images were saved during the procedure. Images were assessed for the presence and severity of IL. Using histopathology as the gold standard, the sensitivity and specificity of endoscopy for diagnosing IL were calculated. RESULTS: Intestinal lymphangiectasia (IL) was diagnosed in 25/51 dogs. Gross endoscopic appearance of the duodenal mucosa had a sensitivity and specificity (95% confidence interval) of 68% (46%, 84%) and 42% (24%, 63%), respectively for diagnosis of IL. Endoscopic images in cases with lymphopenia, hypocholesterolemia, and hypoalbuminemia had a sensitivity of 80%. CONCLUSIONS AND CLINICAL IMPORTANCE: Endoscopic duodenal mucosa appearance alone lacks specificity and has only a moderate sensitivity for diagnosis of IL. Evaluation of biomarkers associated with PLE improved the sensitivity; however, poor specificity for diagnosis of IL supports the need for histopathologic confirmation.

Retrospective comparison of the efficacy of fluconazole or itraconazole for the treatment of systemic blastomycosis in dogs.

BACKGROUND: Itraconazole is recommended for treatment of blastomycosis in dogs. Some evidence suggests that fluconazole might be less hepatotoxic than itraconazole. OBJECTIVES: To compare (1) incidence of clinical remission and death; (2) treatment duration; (3) total drug cost; (4) incidence of relapse; and (5) incidence of increased ALT activities in dogs with blastomycosis treated with fluconazole or itraconazole. ANIMALS: One hundred and forty-four dogs with systemic blastomycosis treated with itraconazole or fluconazole from 1998 to 2008. METHODS: Retrospective case review. Information obtained included signalment, body weight, clinical signs, drug regimen, treatment duration, time to clinical remission, and laboratory results. RESULTS: Neither treatment efficacy between fluconazole (75% remission) and itraconazole (90% remission) nor relapse rate (18% for itraconazole, 22% for fluconazole) was significantly different (P = .13, .75, respectively). Treatment duration was significantly longer for fluconazole (median 183 days) than for itraconazole (138 days; P = .001). Costs for fluconazole (median $1,223) were significantly less than for itraconazole ($3,717; P < .001). Incidence of increased ALT activities was not significantly different between groups (17% [3/18] for fluconazole, 26% [6/23] for itraconazole; P = .71). CONCLUSIONS: Fluconazole is associated with survival to clinical remission in 75% of dogs with blastomycosis. Although dogs receiving fluconazole were treated longer, drug costs were one-third those of itraconazole. Hepatotoxicosis, as estimated by increases in serum ALT activity, can be observed with similar incidence for both drugs.

Television exposure in children after a terrorist incident.

This study examined the influence of bomb-related television viewing in the context of physical and emotional exposure on posttraumatic stress symptoms--intrusion, avoidance, and arousal--in middle school students following the 1995 Oklahoma City bombing. Over 2,000 middle school students in Oklahoma City were surveyed 7 weeks after the incident. The primary outcome measures were the total posttraumatic stress symptom score and symptom cluster scores at the time of assessment. Bomb-related television viewing in the aftermath of the disaster was extensive. Both emotional and television exposure were associated with posttraumatic stress at 7 weeks. Among children with no physical or emotional exposure, the degree of television exposure was directly related to posttraumatic stress symptomatology. These findings suggest that television viewing in the aftermath of a disaster may make a small contribution to subsequent posttraumatic stress symptomatology in children or that increased television viewing may be a sign of current distress and that it should be monitored. Future research should examine further whether early symptoms predict increased television viewing and/or whether television viewing predicts subsequent symptoms.

Do post-traumatic stress disorder symptoms worsen during trauma focus group treatment?

Male inpatient veterans with chronic combat-related post-traumatic stress disorder (PTSD) participated in trauma focus group treatment and were assessed immediately before group participation and after group completion at time of discharge. Standard measures of core PTSD symptoms, depression, and anxiety were used. In addition, changes in PTSD symptoms were tracked on a weekly basis for the duration of group participation. Results indicated that a single direct elicitation of war-related traumatic memories in a group setting was not associated with symptom worsening. However, veterans also did not show improvement in symptoms severity. Possible reasons for this lack of impact are discussed along with implications for future treatment design and evaluation.

Severe impairment of leukocyte rolling in venules of core 2 glucosaminyltransferase-deficient mice.

Leukocyte capture and rolling are mediated by selectins expressed on leukocytes (L-selectin) and the vascular endothelium (P- and E-selectin). To investigate the role of core 2 beta1-6-N-glucosaminyltransferase (C2GlcNAcT-I) for synthesis of functional selectin ligands in vivo, leukocyte rolling flux and velocity were studied in venules of untreated and tumor necrosis factor-alpha (TNFalpha)-pretreated autoperfused cremaster muscles of C2GlcNAcT-I-deficient (core 2(-/-)) and littermate control mice. In untreated core 2(-/-) mice, leukocyte rolling was dramatically reduced with markedly increased rolling velocities (81 +/- 4 microm/s vs 44 +/- 3 microm/s). The reduced rolling in core 2(-/-) mice was due mainly to severely impaired binding of P-selectin to P-selectin glycoprotein ligand-1 (PSGL-1). Some rolling remained after blocking PSGL-1 in controls but not in core 2(-/-) mice. In TNFalpha-pretreated mice, rolling was markedly reduced in core 2(-/-) mice owing to impaired P-selectin- and E-selectin-mediated rolling. Rolling velocities in core 2(-/-) mice treated with an E-selectin-blocking monoclonal antibody (59 +/- 4 microm/s) were significantly higher than in controls (14 +/- 1 microm/s), which provides further evidence for the severe impairment in P-selectin-mediated rolling. In conclusion, P-selectin ligands including PSGL-1 are largely C2GlcNAcT-I dependent. In addition, E-selectin-mediated rolling in vivo is partially dependent on the targeted C2GlcNAcT-I. (Blood. 2001;97:3812-3819)

Intercellular adhesion molecule-1 is required for chemoattractant-induced leukocyte adhesion in resting, but not inflamed, venules in vivo.

The leukocyte integrins LFA-1 and Mac-1 bind to endothelial intercellular adhesion molecule-1 (ICAM-1). Leukocyte adhesion induced by micropipette injection of formylmethionylleucylphenylalanine (fMLP) or macrophage inflammatory protein 2 (MIP-2) next to a venule in the exteriorized mouse cremaster muscle was almost completely blocked after intravenous injection of the ICAM-1 mAb YN-1. In contrast, after 2-h pretreatment with TNF-alpha, leukocyte adhesion induced in postcapillary venules by fMLP or MIP-2 was not blocked by the ICAM-1 mAb. Leukocyte adhesion was significantly reduced by mAb GAME-46 to CD18 even after TNF-alpha treatment. We conclude that ICAM-1 is necessary for neutrophil adhesion to unstimulated endothelium, but not for adhesion to cytokine-stimulated endothelium. Although ICAM-1 is expressed at high levels after TNF-alpha, ICAM-1 either is not functional or is redundant with other endothelial ligands for beta(2) integrins.

Delayed onset of inflammation in protease-activated receptor-2-deficient mice.

Endothelial surface expression of P-selectin and subsequent leukocyte rolling in venules can be induced by mast cell-derived histamine and binding of thrombin to protease-activated receptor-1 (PAR1). We hypothesized that activation of endothelial PAR2 by mast cell tryptase or other proteases also contributes to inflammatory responses. Leukocyte rolling flux and rolling velocity were assessed by intravital microscopy of the cremaster muscles of wild-type mice following perivenular micropipette injections of a control (LSIGRL) or PAR2-activating (SLIGRL) oligopeptide. Injection of SLIGRL increased mean rolling leukocyte flux fraction from 34 +/- 11 to 71 +/- 24% (p < 0.05) and decreased mean rolling velocity from 63 +/- 29 to 32 +/- 2 micrometer/s (p < 0.05). No significant changes occurred with control peptide injection. To further evaluate the role of PAR2 in inflammatory responses, PAR2-deficient mice were generated by gene targeting and homologous recombination. Perivenular injections of SLIGRL resulted in only a small increase in rolling leukocyte flux fraction (from 21 +/- 8 to 30 +/- 2%) and no change in rolling velocity. Leukocyte rolling after surgical trauma was assessed in 9 PAR2-deficient and 12 wild-type mice. Early (0-15 min) after surgical trauma, the mean leukocyte rolling flux fraction was lower (10 +/- 3 vs 30 +/- 6%, p < 0.05) and mean rolling velocity was higher (67 +/- 46 vs 52 +/- 36 micrometer/s, p < 0.01) in PAR2-deficient compared with control mice. The defect in leukocyte rolling in PAR2-deficient mice did not persist past 30 min following surgical trauma. These results indicate that activation of PAR2 produces microvascular inflammation by rapid induction of P-selectin-mediated leukocyte rolling. In the absence of PAR2, the onset of inflammation is delayed.

Primary lower limb varicosities arising directly from normal deep venous systems: a series report.

Primary lower limb varicosities classically arise from incompetence of the junction of the superficial and the deep venous systems with retrograde flow into the saphenous veins. However, some patients with superficial varicosities have no demonstrable incompetence of the saphenofemoral or saphenopopliteal junctions. In this study, we examined 52 limbs with primary varicose disease in whom saphenofemoral and saphenopopliteal incompetence had been excluded (clinically and with the hand-held Doppler) using a duplex ultrasound scan. Seventeen (33%) of the limbs had superficial varicosities despite normal long and short saphenous veins. The varicosities in 12 of these legs originated from groin veins, while those in the remaining 5 limbs communicated directly with normal deep veins. In this latter group of limbs, the superficial varicosities were found on the lateral aspect of the thighs only. Primary varicosities arising from normal deep venous systems have not been previously described, and are relatively rare (1.0% of patients referred to our clinic). As this complex venular anatomy was only detected on duplex scanning, we conclude that this study provides further evidence of the need for this imaging modality in patients with varicose disease of uncertain origin and/or those with an unusual distribution of superficial varicosities.

The selective use of duplex scanning in the pre-operative assessment of primary and uncomplicated varicose veins identifies patients with 'early' morphological disease.

The standard management of primary lower limb varicosities (stripping of the long saphenous vein (LSV) with avulsion of the varicosities) is based on the assumption that the disease originates from primary valvular insufficiency and incompetent perforating veins. It has recently been suggested that the LSV may be spared in patients with superficial varicosities without incompetence of this vein, i.e., early disease. However, pre-operative identification of suitable patients for conservative surgery has proved difficult. In this study, we employed selective duplex scanning in cases with primary varicosity in whom sapheno-femoral and sapheno-popliteal incompetence had been excluded both clinically and with the hand-held Doppler (52 limbs [10% of new referrals]). We found that the varicosities in these limbs were of 3 types: (a) those arising independent of superficial vein incompetence (Type 1); (b) those associated with segmental LSV incompetence (Type 2); (c) those in whom incompetence of the sapheno-femoral junction and LSV was missed (Type 3). We therefore suggest that long saphenous varicosity may progress from Type 1 through to Type 3 with each type representing an increase in severity of the disease. We suggest that selective use of duplex scanning will assist in identifying those patients with early stages of the disease who can then be treated effectively with LSV-sparing surgery.

Clinical needs assessment of middle and high school students following the 1995 Oklahoma City bombing.

OBJECTIVE: This clinical assessment was designed to identify middle and high school students in need of formal evaluation for posttraumatic response symptoms following the 1995 bombing of the Alfred P. Murrah Federal Building in Oklahoma City. METHOD: A clinical needs assessment instrument was developed and administered to grade 6 through 12 students 7 weeks after the bombing (N = 3,218). RESULTS: More than 40% of the students reported knowing someone injured, and more than one-third reported knowing someone killed in the blast. Posttraumatic stress symptoms at 7 weeks significantly correlated with gender, exposure through knowing someone injured or killed, and bomb-related television viewing. CONCLUSIONS: This study documents the intensity of community exposure to the bombing and the lingering symptoms of stress. The assessment was used in planning for clinical service delivery, training professional responders, and supporting funding requests.

A test of behavioral family therapy to augment exposure for combat-related posttraumatic stress disorder.

This study tested a family-based skills-building intervention in veterans with chronic combat-related posttraumatic stress disorder (PTSD). Veterans and a family member were randomly assigned to 1 of 3 conditions: (a) waiting list, (b) 18 sessions of twice-weekly exposure therapy, or (c) 18 sessions of twice-weekly exposure therapy followed by 16 sessions of behavioral family therapy (BFT). Participation in exposure therapy reduced PTSD positive symptoms (e.g., reexperiencing and hyperarousal) but not PTSD negative symptoms. Positive symptom gains were maintained at 6-month follow-up. However, participation in BFT had no additional impact on PTSD symptoms.

Posttraumatic stress disorder in a national sample of female and male Vietnam veterans: risk factors, war-zone stressors, and resilience-recovery variables.

Relationships among pretrauma risk factors (e.g., family instability, childhood antisocial behavior), war-zone stressors (e.g., combat, perceived threat), posttrauma resilience-recovery variables (e.g., hardiness, social support), and posttraumatic stress disorder (PTSD) symptom severity were examined. Data from a national sample of 432 female and 1,200 male veterans were analyzed using structural equation modeling. For both genders, direct links to PTSD from pretrauma, war-zone, and posttrauma variable categories were found; several direct associations between pretrauma and posttrauma variables were documented. Although war-zone stressors appeared preeminent for PTSD in men, posttrauma resilience-recovery variables were more salient for women. Researchers, policymakers, and clinicians are urged to take a broad view on trauma and its sequelae, especially regarding possible multiple exposures over time and the depletion and availability of important resources.

Elevated lipid levels in Vietnam veterans with chronic posttraumatic stress disorder.

BACKGROUND: Elevated cholesterol levels have been reported in panic disorder and anger attacks, but not major depression. No data have been reported in posttraumatic stress disorder (PTSD). METHODS: Seventy-three male Vietnam veterans with chronic (PTSD) had serum lipid screening upon entry to a 90-day inpatient program. RESULTS: Elevated cholesterol, low-density lipoprotein, triglycerides, and reduced high-density lipoprotein, were frequent in Vietnam veterans with chronic PTSD and are significant risk factors for coronary artery disease. CONCLUSIONS: Routine lipid screening may be warranted in this at-risk population. Altered lipid levels may result from activation of the noradrenergic system.

Reoperation for recurrent saphenofemoral incompetence: a prospective randomised trial using a reflected flap of pectineus fascia.

OBJECTIVE AND DESIGN: in 1978 Sheppard described using a flap of pectineus fascia in an attempt to reduce the further development of neovascularised veins at the saphenofemoral junction. The perceived benefits of this manoeuvre have not been tested by a prospective randomised trial. MATERIALS AND METHODS: consecutive patients with symptomatic recurrent varicose veins referred to a single consultant were examined for evidence of further reflux from the saphenofemoral junction. This was subsequently confirmed in forty limbs (thirty-seven patients) by descending venography. All had features of a neovascularised segment. These patients were treated by complete exposure and ligation of the recurrences arising from the common femoral vein, with or without the placement of a flap of pectineus fascia (prospectively randomised). The patients were assessed a minimum of eighteen months later by both clinical examination and duplex ultrasound scanning. RESULTS: six patients were lost to follow-up. This left seventeen limbs remaining in each half of the study. The characteristics in each group were broadly matched. CONCLUSIONS: this study failed to demonstrate any apparent benefit from the application of a flap of pectineus fascia. Most patients showed evidence of re-recurrence arising from the common femoral vein.